Using isogenic E. coli strains and in vitro models of infection, we have demonstrated that a relationship exist between the presence of the ColV plasmid and increased E. coli pathogenicity. We propose to study the genetic and physical structure of the plasmid ColV in order to advance our understanding of E. coli disease. We will be especially concerned with the analysis of ColV encoded gene products that mediate pathogenicity functions, i.e., resistance to phagocytosis, serum resistance, and iron uptake. We will also study the interaction between these ColV encoded gene products and the immune system of the host. To ascertain the clinical relevance of those properties, we will use clinical isolates differing in their expression of ColV-coded functions and we will test their pathogenicity in vitro and in vivo. To accomplish these aims, we will use the methodology of bacterial genetics, molecular cloning, and immunology, associated to in vitro and in vivo models of infection. The information obtained will be relevant to current efforts to prevent E. coli disease and to our better understanding of the pathogenesis of E. coli infections.